The general aim of this research is to elucidate further the contribution of cytotoxic oxygen metabolites generated by the myocardium to ischemia/reperfusion-mediated damage. Much of the work focuses on adult myocardium; selected experiments assess differences between adult and neonatal myocardium in terms of oxidant contribution to damage. The experiments incorporate, where possible, correlative functional, biochemical, and morphologic approaches. AIM 1 is to investigate with histochemistry and electron microscopy, the sites, pathways, and time-courses of oxidant (primarily H202) production. This helps test the fundamental hypothesis that H202 generated by the myocardium contributes to ischemic damage. AIM 2 is to assess the activity of aldehyde exidase (AO) in nonischemic and ischemic-reperfused adult hearts. This enzyme may be a source of oxidants, and through its metabolism of malondialdehyde it could be a participant in a vicious cycle of oxidative damage to the ischemic heart. AIM 3 is to assess biochemical mechanisms by which allopurinol acts in hearts that are allegedly devoid of its target enzyme, xanthine oxidase, either to produce beneficial or deleterious effects in the setting of ischemia. AIM 4 is to assess the relative roles of catalase and glutathione peroxidase as pathways for degrading H202 in ischemic adult hearts. The overall significance is that a better understanding of pathophysiologic mechanisms will benefit future research on myocardial protection.